Testing hypotheses of aging in long-lived mice of the genus Peromyscus: association between longevity and mitochondrial stress resistance, ROS detoxification pathways, and DNA repair efficiency

In the present review we discuss the potential use of two long-lived mice of the genus Peromyscus—the white-footed mouse (P. leucopus) and the deer mouse (P. maniculatus) maximum lifespan potential ～8 years for both—to test predictions of theories about aging from the oxidative stress theory, mitochondrial theory and inflammatory theory. Previous studies have shown that P. leucopus cells exhibit superior antioxidant defense mechanisms and lower cellular production of reactive oxygen species (ROS) than do cells of the house mouse, Mus musculus (maximum lifespan ～3.5 years). We present new data showing that mitochondria in P. leucopus cells produce substantially less ROS than mitochondria in M. musculus cells, and that P. leucopus mitochondria exhibit superior stress resistance to those of M. musculus. We also provide evidence that components of the DNA repair system (e.g., pathways involved in repair of DNA damage induced by γ-irradiation) are likely to be more efficient in P. leucopus than in M. musculus. We propose that mitochondrial stress resistance, ROS detoxification pathways and more efficient DNA repair contribute to the previously documented resistance of P. leucopus cells toward oxidative stress-induced apoptosis. The link between these three pathways and species longevity is discussed.     

Reversible and repeatable phase transition at a negative temperature regime for doped and co-doped spin coated mixed valence vanadium oxide thin films

Smooth, uniform mixed valance vanadium oxide (VO) thin films are grown on flexible, transparent Kapton and opaque Al6061 substrates by the spin coating technique at a constant rpm of 3000. Various elements e.g., F, Ti, Mo and W are utilized for doping and co-doping of VO. All the spin coated films are heat treated in a vacuum. Other than the doping elements the existence of only V⁴⁺ and V⁵⁺ species is noticed in the present films. Transmittance as a function of wavelength and the optical band gap are also investigated for doped and co-doped VO thin films grown on a Kapton substrate. The highest transparency (∼75%) is observed for the Ti, Mo and F (i.e., Ti–Mo–FVO) co-doped VO system while the lowest transparency (∼35%) is observed for the F (i.e., FVO) doped VO system. Thus, the highest optical band gap is estimated as 2.73 eV for Ti–Mo–FVO and the lowest optical band gap (i.e., 2.59 eV) is found for the FVO system. The temperature dependent phase transition characteristics of doped and co-doped VO films on both Kapton and Al6061 are studied by the differential scanning calorimetry (DSC) technique. Reversible and repeatable phase transition is noticed in the range of −24 to −26.3 °C.

Smooth, uniform mixed valance vanadium oxide (VO) thin films are grown on flexible, transparent Kapton and opaque Al6061 substrates by the spin coating technique at a constant rpm of 3000.     

Transcatheter closure of coronary artery fistulas

BACKGROUND: Transcatheter closure of coronary artery fistulas has emerged as a successful alternative to surgery. We describe various techniques and short-term findings in 15 patients who were taken up for transcatheter closure of these fistulas. METHODS AND RESULTS: Fifteen patients (aged 2-55 years; 12 males) with coronary artery fistulas underwent percutaneous transcatheter closure between June 1997 and December 2002. Site of origin of these fistulas were: right coronary artery in 7, left anterior descending coronary artery in 4, left main coronary artery in 2 and left circumflex coronary artery in 2 patients. Drainage site of these fistulas were: right ventricle in 9, right atrium in 4 and pulmonary artery in 2 patients. Out of these 15 fistulas, 14 were congenital and one was iatrogenically produced following inadvertent cutting balloon angioplasty of a septal perforator in a patient with chronic total occlusion of left anterior descending coronary artery. Various occlusion devices used to close these fistulas were: conventional metallic coils in 10, floppy tips of coronary angioplasty guidewires in 2, Amplatzer duct occluder in 1 and Amplatzer septal occluder in 2 patients. One of our patients had a coronary artery fistula draining by two openings into the right atrium, both of which were successfully closed using 2 Amplatzer duct occluders. Check angiogram after the procedure revealed complete occlusion in 13 (86.6%) and small residual flow in 2 patients. Follow-up studies at 3-55 months (mean 18 months) showed complete abolition of shunt in all patients with no evidence of recanalization leading to recurrence of shunt. CONCLUSION: Transcatheter closure of coronary artery fistulas is feasible and safe in the anatomically suitable vessels. Use of floppy tips of coronary angioplasty guidewires reduces the cost of the procedure significantly. which is an important consideration in developing countries like India.     

The Effect of 6 versus 9 Years of Zoledronic Acid Treatment in Osteoporosis: A Randomized Second Extension to the HORIZON‐Pivotal Fracture Trial (PFT)

While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly?Pivotal Fracture Trial (HORIZON?PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer‐term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double‐blind study, 190 women were randomized to Z9 (n = 95) and Z6P3 (n = 95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was ?0.54% in Z9 vs. ?1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: ?0.37%, 1.93%; p = 0.183). BTMs showed small, non‐significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non‐serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. © 2015 American Society for Bone and Mineral Research.     

Inflammatory Myofibroblastic Tumor Arising in the Pancreatic Head: a Rare Case Report

Inflammatory myofibroblastic tumor (IMT) is a rare neoplastic lesion with tendency toward local aggressive behavior and recurrence. It is primarily a visceral and soft tissue tumor; however, involvement of pancreas is extremely unusual. A localization in the pancreas needs differentiation from other tumors and chronic pancreatitis. We report a case of inflammatory myofibroblastic tumor arising in pancreatic head in a 32-year-old female who underwent Whipple’s procedure.     

Has Dialysis Payment Reform Led to Initial Racial Disparities in Anemia and Mineral Metabolism Management?

Implementation of the Medicare ESRD prospective payment system (PPS) and changes to dosing guidelines for erythropoiesis-stimulating agents (ESAs) in 2011 appear to have influenced use of injectable medications among dialysis patients. Given historically higher ESA and vitamin D use among black patients, we assessed the effect of these policy changes on racial disparities in the management of anemia and mineral metabolism. Analyses used cross-sectional monthly cohorts for a period-prevalent sample of 7384 maintenance hemodialysis patients at 132 facilities from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Practice Monitor. Linear splines with knots at each policy change were used in survey-weighted regressions to estimate time trends in hemoglobin (Hgb), erythropoietin (EPO) dose, intravenous (IV) iron dose, ferritin, transferrin saturation (TSAT) concentration, parathyroid hormone (PTH), IV vitamin D dose, cinacalcet use, and phosphate binder use. From August 2010 to December 2011, mean Hgb declined from 11.5 to 11.0 g/dl (P<0.001), mean EPO dose declined from 20,506 to 14,777 U/wk (P<0.001), and mean serum PTH increased from 340 to 435 pg/ml (P<0.001). No meaningful differences by race were observed regarding the rates of change of management practices or laboratory measures (all P>0.21). Mean EPO and vitamin D dose and serum PTH levels remained higher in blacks. Despite evidence that anemia and mineral metabolism management practices have changed significantly over time, there was no immediate indication of racial disparities resulting from implementation of the PPS or ESA label change. Further studies are needed to examine effects among patient and facility subgroups.     

The evaluation of ergonomic risk factors among meat cutters working in Jabalpur,India

Background:

Manual meat cutters in India are at high risk of work-related musculoskeletal disorders (WMSDs) for a variety of reasons including holding awkward postures, repetitive forceful exertions, and inadequate rest. This is the first study of its kind to investigate the nature and magnitude of WMSDs among manual meat cutters in India.

Objective:

The aim of this study was to measure the ergonomic risk factors for WMSDs among adult male manual meat cutters working in Jabalpur, India.

Methods:

We used direct observation, activity analysis, questionnaires, interviews, photography, and video to measure the quantitative ergonomic risk factors.

Results:

Ovako working posture analysis indicated high scores (four for the back in peeling, six for the arms in cutting, and six for the arms during mincing tasks). Rapid entire body assessment method (REBA) scores were also high at 10/10 for deboning and mincing tasks, all associated with repetitive movements of the arms and awkward posture of the upper part of the body.

Conclusions:

The study indicates that most tasks for meat cutters fall in the high-risk category for occupational injury. Results suggest that ergonomic interventions that address retooling and workstation and process redesign would be useful in reducing the number of injuries.     

An in vitro model for grafting of hematopoietic stem cells predicts bone marrow reconstitution of myeloablative mice

Homing and engraftment of hematopoietic stem cells (HSCs) to bone marrow (BM) is a complex process that primarily depends on the cell-surface expression of adhesion molecules on stem and stromal cells. Here we report an in vitro model for homing of stem cells on pre-established stromal layer; the stroma-adhered cells were found to engraft, multiply, and differentiate in BM of age-matched mice. In vitro study revealed that initially the adhesion of BM cells on irradiated stroma was increased with time, and it attained a peak at 2 h of contacts. During that time, 44.1 +/- 6.5% (n = 8) cells were adhered, and this value was maintained up to 6 x 10(6) cells. The adhered cell fraction was enriched by 3.9-, 2.5-, and 1.7-fold Sca-1, colony forming cell (CFC), and cobblestone area forming cells (CAFC), respectively, as compared to the fresh BM cells. These adhered cells homed to BM with an engraftment efficiency of 11.8 +/- 2.5% (n = 6). The homed cells reconstituted BM of myeloablative mice by self-renewing and differentiating into myeloid cells. Overall, a simple in vitro model system has been described to study homing and grafting of HSCs that can be deployed to any possible experimental conditions to investigate the interactions between stromal and stem cells.     

Factor VIII gene polymorphisms in North Indian population: a consensus algorithm for carrier analysis of hemophilia A

BACKGROUND: Hemophilia A, an X-linked recessive disorder, has the prevalence of 1 male per 7000 of the male population in the Northern states of India. The aim of the present study was to analyze the polymorphisms of the factor VIII gene in a sample population comprised of 22 families (112 persons) in order to formulate an algorithm that would be informative and accurate, yet cost-effective for carrier diagnosis. METHODS: Polymerase chain reaction was used to study the polymorphisms of two intragenic restriction fragment length polymorphic sites (recognized by BclI and HindIII) and an extragenic variable number tandem repeat (VNTR) locus (St14). RESULTS: Fifty-eight percent of the women tested were heterozygous for the BclI restriction fragment length polymorphism (RFLP) (significantly high compared to earlier reports), signifying the usefulness of this marker in carrier detection. About 64% of the families from the target population could be diagnosed using this marker alone. The other intragenic HindIII RFLP site showed a heterozygosity rate of 43% in women, and was effective in diagnosing 50% of the families studied. The population prevalence for '+' alleles of BclI and HindIII were 68% and 33%, respectively. About 88% of the women tested were heterozygous for the St14 locus, and 83% of the families could be diagnosed using this marker alone. The 1390- and 1300-bp alleles were most prevalent, while novel polymorphisms of 1500 and 1345 bp were detected. CONCLUSIONS: Based on the above data, we suggest screening hemophilic families first for BclI polymorphism, followed by an analysis for HindIII polymorphism in case of homozygosity at the BclI site. When both were noninformative, analysis of St14 locus would be necessary.